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Lyme DiseaseAka: Borrelia Burgdorferi, Lyme borreliosis

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Epidemiology
1. Incidence
  1. Most common tick borne disease in North America
  2. Cases in U.S. in 1994: 13,000
  3. Cases in U.S. in 1999: 16,000
  4. Annual Incidence in endemic areas: 0.5%
  5. Peak occurrence in North America: May to August
2. Geographic areas involved
  1. Worldwide cases have occurred in Canada, Europe, Asia
  2. U.S. cases clustered in Northeast and Upper Midwest
    1. High-Risk States
      1. Connecticut (Nantucket County: 1198 case/100,000)
      2. Delaware
      3. Maryland
      4. New Jersey
      5. New York
      6. Pennsylvania
      7. Rhode Island
      8. Wisconsin
    2. Moderate-Risk States
      1. Maine
      2. Massachusetts
      3. Minnesota
      4. New Hampshire
      5. Vermont
  3. Reference
    1. (1995) MMWR Morb Mortal Wkly Rep 44:459
3. Concurrent Lyme and Babesiosis is common (n=1156)
  1. Coinfection occurs 10% in southern New England
  2. Reference
    1. Krause (1996) JAMA 275:1657
History
1. 1975: Lyme Disease first reported in Lyme, Connecticut
  1. Cluster of new cases of arthritis in children
2. 1981: Borrelia Burgdorferi identified as cause
Pathophysiology
1. Borrelia Burgdorferi
  1. Causative Spirochete organism
  2. Carried by white tail deer
  3. Transmitted by Deer Ticks
  4. Natural reservoirs
    1. White-footed mouse and other small mammals
2. Deer Ticks or Black Legged Tick
  1. Vectors for several infections
    1. Borrelia Burgdorferi (Lyme Disease)
    2. Babesia microti (Babesiosis)
    3. Anaplasma phagocytophila (causes HGA)
      1. Prior: Ehrilichia phagocytophila (Ehrlichiosis)
  2. Tick species
    1. Ixodes Scapularis
    2. Ixodes pacificus
3. Deer Ticks have two year life cycle:
  1. Egg to Larva
  2. Larva to Nymph
  3. Nymph to Adult
4. In endemic areas:
  1. Nymphs infected: 12-30%
  2. Adult ticks infected: 28-65%
5. Nymphs outnumber adult ticks 10:1
  1. Nymphs are responsible for 90% of Lyme Disease cases
  2. Nymphs must attach for >36-48 hours for transmission
  3. Adults must attach for >48-72 hours for transmission
Differential Diagnosis of Erythema Migrans
1. See Annular Lesion
2. Cellulitis
3. Tinea Corporis
4. Granuloma Annulare
5. Arthropod Bite reaction
  1. Usually <5 cm, painful, develops in minutes to hours
  2. Rash is often pruritic
  3. Resolves within 48 hours without viral Symptoms
Signs and Symptoms: Stage 1 (Early localized disease)
1. Less than 20% of people recall tick bite
2. Localized Erythema Chronicum Migrans at tick bite site
  1. See Erythema Migrans
3. Mild constitutional Symptoms
  1. Fever (also consider HGA or Babesiosis)
  2. Malaise
  3. Arthralgias
  4. Headache
  5. Neck stiff
  6. Other skin lesions
Signs and Symptoms: Stage 2 (Early disseminated disease)
1. Cardiac
2. Arthritis
3. Neurologic
  1. Bell's Palsy (or other Cranial Nerve Neuropathy)
  2. Lymphocytic Meningitis or Encephalitis
  3. Pseudotumor Cerebri
4. Miscellaneous
  1. Regional Lymphadenopathy or General Lymphadenopathy
  2. Conjunctivitis
  3. Iritis
  4. Hepatitis
  5. Microscopic Hematuria
  6. Proteinuria
Signs and Symptoms: Stage 3 (Late chronic disease)
1. Large Joint Arthritis (especially knee)
  1. Occurs in 10% of untreated Lyme Disease
  2. Monoarticular or asymmetric Oligoarticular Arthritis
2. Neurologic
  1. Subacute encephalopathy
  2. Axonal Polyneuropathy
  3. Leukoencephalopathy
Precautions
1. Information based on IDSA and CDC guidelines
  1. IDSA: Infectious Disease Society of America
  2. IDSA is considered standard of care recommendations
  3. Tertiary centers (e.g. Mayo) follow these guidelines
2. Other guidelines (e.g. ILADS) are not reviewed here
  1. ILADS: International Lyme and Associated Diseases
  2. ILADS guidelines are considered controversial
Labs
1. See Lyme Test
2. Lyme Titer (ELISA) - first tier testing
  1. Not needed if Erythema Migrans in endemic areas
  2. False Positive rate is high
  3. Confirmation is by Lyme Western Blot testing
3. Cerebrospinal fluid (CSF) for Lyme Disease
  1. Indicated for neurologic symptoms
4. Tests to identify other causes
  1. Erythrocyte Sedimentation Rate (ESR) elevated
  2. Complete Blood Count (CBC)
    1. Leukocytosis
    2. Anemia
  3. Antinuclear Antibody (ANA) negative
  4. Rheumatoid Factor (RF) negative
Management: Deer Tick bite
1. See Deer Tick Bite (includes antibiotic prophylaxis)
Management: Early Lyme Disease and Erythema Migrans
1. Duration of therapy: 21 days
2. Doxycycline (Avoid in pregnancy and under age 9 years)
  1. Adult: 100 mg PO twice daily
  2. Child (age >8): 4 mg/kg divided bid (max 100 mg/dose)
3. Amoxicillin
  1. Adult: 500 mg PO three times daily
  2. Child: 50 mg/kg/day divided tid (max 500 mg/dose)
4. Cefuroxime (Ceftin)
  1. Adult: 500 mg PO twice daily
  2. Child: 30 mg/kg/day divided bid (max: 500 mg/dose)
5. Macrolides are not recommended due to lower efficacy
  1. Use only if allergic to above agents
  2. Azithromycin
    1. Adult: 500 mg daily for 10 days
    2. Child: 10 mg/kg daily for 10 days
  3. Clarithromycin
    1. Adult: 500 mg PO bid for 21 days
    2. Child: 7.5 mg/kg (max: 500 mg/dose) PO bid x21 days
  4. Erythromycin
    1. Adult: 500 mg PO qid for 21 days
    2. Child: 12.5 mg/kg (max 500 mg/dose) PO qid x21 days
6. If suspect Cellulitis versus Erythema Migrans
  1. Adult: Augmentin 500 mg PO tid
  2. Child: Augmentin 50 mg/kg/day divided tid
7. Antibiotics to avoid (not indicated)
  1. Avoid First Generation Cephalosporins (Cephalexin)
  2. Avoid Fluoroquinolones
  3. Avoid Septra, Metronidazole, Penicillin G
Management: Neurologic Disease
1. Facial Nerve Palsy
  1. Doxycycline dosed as above for 21 days
  2. Amoxicillin dosed as above for 21 days
2. More serious CNS disease
  1. Ceftriaxone (Rocephin)
    1. Adult: 2g/day IV for 14 to 28 days
    2. Child: 75-100 mg/kg/day IV for 14 to 28 days
  2. Cefotaxime (Claforan)
    1. Adult: 2g q8 hours for 14 to 28 days
    2. Child: 150-200 mg/kg/day divided q8h IV, 14-28 days
  3. Penicillin G
    1. Adult: 20-24 MU/day IV for 14 to 28 days
    2. Child: 300,000 U/Kg/day IV for 14 to 28 days
Management: Cardiac Disease
1. Mild (First Degree Atrioventricular Block)
  1. Doxycycline dosed as above for 21-28 days
  2. Amoxicillin dosed as above for 21-28 days
2. More Serious Cardiac disease
  1. Ceftriaxone (Rocephin)
    1. Adult: 2g/day IV for 21 days
    2. Child: 75-100 mg/kg/day IV for 21 days
  2. Penicillin G
    1. Adult: 24 MU/day IV for 21 days
    2. Child: 300,000 U/Kg/day IV for 21 days
Management: Arthritis
1. Oral
  1. Doxycycline dosed as above for 30-60 days
  2. Amoxicillin dosed as above for 30-60 days
2. Parenteral
  1. Ceftriaxone (Rocephin) dosed as above for 14-28 days
  2. Penicillin G dosed as above for 14-28 days
Prevention
1. See Prevention of Vector-borne Infection
2. Lyme Vaccine (No longer available in U.S.)
3. Insecticide
  1. Acaricide applied to residential areas in mid May
  2. Provides 97% protection during peak nymph activity
Resources
1. IDSA Guidelines
  1. http://www.journals.uchicago.edu/IDSA/guidelines/
Reference
1. Steere in Mandell (2000) Infectious Disease, p. 2504-14
2. (2000) Med Lett Drugs Ther 42(1077):37
3. (1997) Med Lett Drugs Ther :
4. Fix (1998) JAMA 279(3):206
5. Rahn (1998) Postgrad Med 103(5):51
6. Still (1997) Postgrad Med 102(1):65
7. Verdon (1997) Am Fam Physician 56(1):427
8. Nadelman (1995) Am J Med 98:15S
9. Stanek (2003) Lancet 362:1639
10. Wormser [AU] AND 2006 [DP] AND Clin Infect Dis [TA] " class="LinkRef">Wormser (2006) Clin Infect Dis 43:1089

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Lyme DiseaseAka: Borrelia Burgdorferi, Lyme borreliosis

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